Tph cells are expanded in IgA vasculitis nephritis

Ectopic lymphoid structures (ELSs) contribute to maintaining the chronic inflammation process of IgA vasculitis nephritis (IgAVN) and are associated with a more severe disease course. PD-1^hiCXCR5⁻CD4⁺ T peripheral helper (Tph) cells are recognized as the main CD4⁺ T cells that contribute to B cell immune responses and antibody production in ELSs. However, the role of Tph cells in the pathogenesis of IgAVN is currently unknown. Here, we showed that the frequency of circulating Tph (cTph) cells was higher in IgAV patients compared to healthy controls, and higher among those with nephritis than those without nephritis. In addition, the frequency of cTph cells was positively correlated with 24-hour urine protein and urine red blood cell levels in IgAVN patients. cTph cells from IgAVN patients expressed high levels of activation makers and B cell helper markers, including ICOS, Tigit, IL-21, and CXCL13, and induced memory B cell differentiation in vitro in the presence of IL-21. Taken together, these results suggest that PD-1^hiCXCR5⁻CD4⁺ cTph cells are involved in the pathogenesis of IgAVN by inducing B cell differentiation through IL-21, serving as a promising target for the treatment of IgAVN.